The present invention relates methods of reducing, inhibiting or eliminating malodor in dermatological compositions containing sulfur. The invention also relates to sulfur containing dermatological compositions that produce little or no malodor.
Elemental sulfur (in a variety of forms), sulfides, sulfites and/or mercaptans are commonly used ingredients in dermatologic or cosmetic compositions for the treatment of a variety of dermatological conditions. Various forms of sulfur, sulfides, sulfites and mercaptans are believed to have anti-microbial, anti-fungal, anti-parasitic and anti-inflammatory functions. Sulfur, in its various forms, sulfides, sulfites and mercaptans are believed to kill parasites, such as mites, and microorganisms, including but not limited to bacteria, and thereby also suppress their endotoxins and exotoxins, all of which can be irritants that may contribute to the provocation of itching, redness and irritation that are characteristics of rosacea. Further, sulfur causes keratolytic/sloughing activity and may, therefore, remove irritants that are held by the sloughed cells, as well as smoothing and soothing the skin.
Unfortunately, sulfur containing compositions may be, or may become, malodorous over time yielding a characteristic xe2x80x9crotten egg odor.xe2x80x9d This malodor is believed to be caused by the formation of volatile sulfur-containing compounds, for example, hydrogen sulfide (H2S), sulfur dioxide (SO2) and various other volatile sulfides and mercaptans. These odor causing compounds can be generated even by sulfur compounds which are not themselves odor causing. As a result of the unpleasant odor, patients are sometimes reluctant to apply such compositions directed by their physician or pharmacist. Such poor patient compliance can seriously diminish the effectiveness of a treatment regimen.
The prior art has used a variety of techniques to try to deal with the odor associated with sulfur containing compositions. For example, U.S. Pat. No. 4,338,301 describes the use of clays to control the odor of alkaline sulfur containing compositions. Another approach to odor content is to include compounds that react ionically or covalently with odor causing sulfur compounds to reduce or eliminate offensive odors. Examples of agents that can tie-up volatile compounds, such as SO2, H2S, xe2x80x94SH compound, sulfur include heavy metal oxide and related compounds such as zinc oxide, titanium oxide that can form non-volatile or weakly volatile sulfides such as Zinc sulfide, or telamursulfide and the like. Other approaches include the use of scents or perfume to overpower or mask the offensive odor. Sometimes, formulators forgo the use of particular sulfur compounds that generate strong odors, even though they are otherwise desirable. None of these techniques have been entirely satisfactory.
Accordingly, there is a need for improved methods for reducing, inhibiting or eliminating the production of sulfurous malodor in sulfur containing dermatological or cosmetic compositions.
The present invention is directed to a composition comprising a sulfur ingredient and a carrier; wherein the composition has a pH of from about 6.5 to about 8.1. Alternatively, the hydrogen ion concentration of the composition should be no more than 3.16xc3x9710xe2x88x927 and no less than 7.95xc3x9710xe2x88x929.
The present invention is also directed to a method for reducing or inhibiting the production of malodor in sulfur containing dermatological compositions comprising the step of adjusting the pH of the composition to between about 6.5 to about 8.1.
The present invention is also directed to a dermatological composition suitable for topical application to human skin, comprising: at least one sulfur ingredient; and a pharmaceutically acceptable carrier, wherein the composition has a pH of about 6.5 to about 8.1 and the composition exhibits substantially reduced sulfur odor, particularly after aging.
It has been discovered that the occurrence of sulfur malodor in commercially available sulfur containing dermatological and cosmetic compositions may be reduced, inhibited or eliminated by formulating sulfur containing dermatological compositions to minimize the production of volatile sulfur derivatives, initially and as the composition ages. This may be accomplished by selectively incorporating ingredients that result in the sulfur containing composition having a pH from about 6.0 to 8.5, preferably about 7.0 to about 8.1, or by adding acid or base to the composition to bring the pH of the composition within the desired range. It should be noted that, unlike prior art techniques which call for covalent or ionic bonding with the odor causing sulfur compounds, the present invention does not remove or scavenge odor causing entities, but rather renders them less offensive. It is believed that by avoiding these reactions the effectiveness of the composition is preserved or even enhanced. The present invention is broadly applicable to all types and classes of sulfur containing dermatological and cosmetic compositions, including, for example and without limitation, lotions, masks and cleansers.
The present invention is directed to a composition comprising: at least one sulfur containing ingredient; and a pharmaceutically or cosmetically acceptable carrier, wherein the composition has a pH of from about 6.5 to about 8.1, preferably about 7.0 to about 8.1. The present invention is also directed to a method for reducing or inhibiting initially and over time the production of malodor in sulfur containing dermatological compositions comprising the step of adjusting the pH of the composition to between about 6.5 to about 8.1.
Suitable sulfur ingredients are those that are suitable for use in dermatological compositions, including, without limitation, elemental sulfur, sulfides, sulfites and mercaptans and combinations thereof. A preferred sulfur compound is sodium sulfacetamide. As used herein, the term xe2x80x9csulfur containing dermatological compositionxe2x80x9d means any composition that contains elemental sulfur, organic or inorganic sulfides, inorganic sulfites, organic or inorganic mercaptans, or any other and that is used by being applied to the skin or hair of a user.
Forms of elemental sulfur suitable for use in the present invention are those forms of elemental sulfur that are known to be useful in dermatological compositions, including, without limitation, colloidal, coated, enrobed, entrapped, fumed, precipitated, and sublimed sulfur. Elemental sulfur, as that term is used herein, will also be understood by one of ordinary skill in the art to include other transformations, fractions and derivatives of sulfur understood by those of ordinary skill in the art to be useful in dermatological compositions. The preferred form of sulfur for use in the present invention is precipitated sulfur.
Inorganic sulfides suitable for use in connection with the present invention are those inorganic sulfides known to be useful in dermatological compositions and include, without limitation, selenium sulfide, sodium thiosulfate as well as those inorganic sulfides having the formula:
RS;
RSH;
xe2x80x83R2S;
RSSR;
or
RSSH,
wherein
R is an inorganic element that can bind ionically or covalently with sulfur.
Organic sulfides suitable for use in connection with the present invention are those organic sulfides known to be useful in dermatological compositions and include, without limitation, those organic sulfides having the formula:
RS;
R2S;
RSH;
Rxe2x80x2SSRxe2x80x2,
or
Rxe2x80x2SSH,
wherein
Rxe2x80x2 is an organic compound and its salts that can bind ionically or covalently with sulfur. Exemplary organic sulfides include, without limitation, sodium thioglycolate (sodium mercaptoacetic acid), gluathione.
Inorganic sulfites suitable for use in the present invention are those inorganic sulfites known to be useful in dermatological compositions, including, without limitation, sulfites and meta bisulfites.
Additional ingredients in these compositions may include, without limitation, solvents, viscosity adjusters compositions, cleansers, propellants, emollients, emulsifiers, moisturizers, preservatives, antioxidants, odor modifiers, fragrances, any other ingredient that might be useful in a dermatologic pr cosmetic composition. For example, antimicrobial agents, antifungal agents, anti-inflammatory agents, immunomodulator or immunosuppressant agents, antiparasitic agents, keratinization modulators, depigmenting agents, antihistamines, antioxidants, analgesics, and any other active ingredient suitable for use in dermatological compositions may be used.
It is known by those of ordinary skill in the art how to identify the sets of ingredients necessary to give a dermatological composition its desired physical and esthetic properties. By way of example only, U.S. Pat. No. 4,847,071, which is incorporated herein by reference, includes a detailed discussion of many of the ingredients used in carriers for dermatological compositions and carriers, such as lotions, creams, oils, gels, etc. U.S. Pat. No. 4,847,071 also includes an extensive discussion of cleaning compositions useful in certain dermatological compositions.
The step of adjusting the pH of the composition may be accomplished by selecting particular ingredients that combine to yield a composition having the target pH. In cases where the selection of ingredients yields a sulfur containing dermatological composition that does not have the target pH, it may be adjusted by adding an acid or base to the composition in an amount sufficient to bring the pH of the composition within the target range. Commonly used acid or bases that may be safely incorporated into a dermatological composition may be used for this purpose. Preferred acids include, without limitation, HCl and citric acid. Preferred bases include, without limitation, NaOH and triethanolamine. The acid or base may be added at any appropriate time during the formulation of the sulfur containing composition.
Suitable antimicrobial agents may include any antimicrobial agents useful in dermatological compositions. Suitable antimicrobial agents include, without limitation, benzoyl peroxide, povidone iodine, hexachlorphene, chlorhexidine, mupirocin, gentimycin, neomycin, bacitracin, polymixin, erythromycin, clindamycin, metronidazole, clarithromycin, silver sulfadiazine, dapsone, zinc pyrithione, cephalosporin, thymol, mafenide acetate, nitrofurazone, generators of nitrix oxide benzyl alcohol, sulfamethoxazole, sulfasalazine, sulfasoxazole, acetylsulfasoxazole and combinations thereof. A preferred set of antimicrobial agents consists of hexachlorphene, mupirocin, gentimycin, neomycin, bacitracin, polymixin, erythomycin, clindamycin, metronidazole, clarithromycin, dapsone, cephalosporin, thymol, mafenide acetate, nitrofurazone, benzyl alcohol, sulfamethoxazole, sulfasalazine, sulfasoxazole, and acetylsulfasoxazole.
Suitable antifungal agents may include any antifungal agents useful in dermatological compositions. Suitable antifungal agents include, without limitation, nystatin, ciclopirox and ciclopirox olamine, griseofulvin, itraconazole, fluconazole, ketoconazole, terbinafine, econazole, benzyl alcohol, undecylenic acid and salts thereof, benzyl benzoate and combinations thereof. Preferred antimicrobial agents are ciclopirox and ciclopirox olamine, nystatin, griseofulvin, itraconazole, fluconazole, ketoconazole, terbinafine, econazole, benzyl alcohol, and benzyl benzoate.
Suitable anti-inflammatory agents may include any anti-inflammatory agents useful in dermatological compositions. Suitable anti-inflammatory agents include, without limitation, aldometasone, amcenonide, betamethasone, esters of betamethasone, desonide, clobetasole propionate, clocortolone pivilate, triamcinilone acetonide, desoximetasone, dliforosone, mometosone furoate, prednicarbate, fluocinonide, fluocinolone acetonide, hydrocortisone and combinations thereof.
Suitable immunomodulators or immunosuppressants may include any immunomodulators or immunosuppressants useful in dermatological compositions. Suitable immunomodulators or immunosuppressants include, without limitation, cylclosporine, imiquimod, flurouracil, podophilox, podophyllin, and combinations thereof. Preferred immunomodulators or immunosuppressants consists of cylclosporine, imiquimod, and flurouracil.
Suitable antiparasitic agents may include any antiparasitic agents useful in dermatological compositions. Suitable antiparasitic agents include, without limitation, malathion, pediculosides, scabicides, ivermectin, permethrin, pyrethrin, carbamyl, imiquimod, thiabendazol, and combinations thereof. Preferred antiparasitic agents includes consists of pediculosides, scabicides, ivermectin, permethrin, pyrethrin, carbamyl, imiquimod, and thiabenazole.
Suitable keratinzation modulators may include any keratinzation modulators useful in dermatological compositions. Suitable keratinzation modulators include, without limitation, retinol, retinoic acid, retinaldehyde, retinal, retinyl esters, tazarotene and other retinoids, alpha and beta hydroxy acids salicylic acid, resorcinol, retinal esters and combinations thereof. Preferred keratinization modulators are retinol and its derivatives.
Suitable depigmenting agents may include any depigmenting agents useful in dermatological compositions. Suitable depigmenting agents include, without limitation, hydroquinone, monobenzone and azaleic acid, salicylic acid and alpha and beta hydroxy acids, ascorbic acid and ets esters and combinations thereof. Preferred depigmenting agents include hydroquinone, monobenzone and azaleic acid.
Suitable antihistamines may include any antihistamines useful in dermatological compositions such as diphenhydramine.
Suitable antioxidants may include any antioxidants useful in dermatological compositions such as diphenhydramine. Suitable antioxidants include, without limitation, ascorbic acid, its esters and salts and derivatives thereof, vitamins A, D, and K, tocopherol and its derivatives and combinations thereof.
Na2EDT A is defined to mean disodium ethylene diamine tetra acetate. BHT is defined to mean butylated hydroxytoluene. MEA is defined to mean monoethanolamine. PEG-100 is defined to mean polyethylene glycol 100.
The step of selecting one or more additional ingredients from the one or more sets of ingredients and combining the selected ingredients to form a sulfur containing dermatological composition having a pH of about 6.5 to about 8.1, preferably about 7.0 to about 8.1 preferably includes the selection of ingredients based on both their functional properties and their pH. That is, in selecting each ingredient consideration should be given not only to the function that a particular ingredient will impart to the composition, but also to what extent the addition of the requisite amount of that ingredient will affect the pH of the sulfur containing dermatological composition. For example, if one desired to select from a particular set a particular ingredient that will make the pH of the sulfur containing dermatological composition lower than the target pH, then, when selecting other ingredient(s) from the same or different set, one should seek to select ingredient(s) that will offset the effect of the first ingredient. In some cases, the selection process may be very simple requiring only, for example, that 2 different ingredients offset one another. In other cases, the selection process may be very complex requiring the simultaneous consideration of the effect on pH of numerous different ingredients and the quantities in which those ingredients are incorporated into the sulfur containing composition. If the selection of ingredients yields a composition that does not have the desired pH, this can be adjusted by adding an acid (such as hydrochlonic or sulfuric acid) or a base (such as sodium hydroxide, potassium hydroxide, or triethlanolamine) in such quantity as will yield the desired pH. Buffers may also be used to help achieve and maintain this result.
The invention will be explained further by a consideration of the following Examples, which are given solely for the purpose of illustration and are not to be construed as limitations of the present invention since many variations thereof are possible without departing from the scope or spirit of the invention.